N-芴甲氧羰基-脯氨酰-脯氨酸 | 129223-22-9

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 脯氨酸类衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: N-芴甲氧羰基-脯氨酰-脯氨酸
• 中文别名: FMOC-脯氨酰脯氨酸
• 英文名称: Fmoc-Pro-Pro-OH
• 英文别名: (2S)-1-[(2S)-1-(9H-fluoren-9-ylmethoxycarbonyl)pyrrolidine-2-carbonyl]pyrrolidine-2-carboxylic acid
• CAS: 129223-22-9
• 化学式: C₂₅H₂₆N₂O₅
• 分子量: 434.492
• InChiKey: VRAQFWSWKRNOGU-VXKWHMMOSA-N

物化性质

• 沸点：
  677.7±55.0 °C(Predicted)
• 密度：
  1.353±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  87.2
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  密封保存，在-15°C下存储。

制备方法与用途

Fmoc-Pro-OH 是一种脯氨酸衍生物。

反应信息

• 作为反应物：
  描述：

  N-芴甲氧羰基-脯氨酰-脯氨酸 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 L-prolyl-L-proline
  参考文献：
  名称：

  Functional Identification and Structure Determination of Two Novel Prolidases from cog1228 in the Amidohydrolase Superfamily,

  摘要：

  Two uncharacterized enzymes from the amidohydrolase superfamily belonging to cog1228 were cloned, expressed, and purified to homogeneity. The two proteins, Sgx9260c (gi|44242006) and Sgx9260b (gi|44479596), were derived from environmental DNA samples originating from the Sargasso Sea. The catalytic function and substrate profiles for Sgx9260c and Sgx9260b were determined using a comprehensive library of dipeptides and N-acyl derivative of L-amino acids. Sgx9260c catalyzes the hydrolysis of Gly-L-Pro, L-Ala-L-Pro, and N-acyl derivatives of L-Pro. The best substrate identified to date is N-acetyl-L-Pro with a value of k(cat)/K-m of 3 x 10(5) M-1 s(-1). Sgx9260b catalyzes the hydrolysis of L-hydrophobic L-Pro dipeptides and N-acyl derivatives of L-Pro. The best substrate identified to date is N-propionyl-L-Pro with a value of k(cat)/K-m of 1 x 10(5) M-1 s(-1). Three-dimensional structures of both proteins were determined by X-ray diffraction methods (PDB codes 3MKV and 3FEQ). These proteins fold as distorted (beta/alpha)(8)-barrels with two divalent cations in the active site. The structure of Sgx9260c was also determined as a complex with the N-methylphosphonate derivative of L-Pro (PDB code 3N2C). In this structure the phosphonate moiety bridges the binuclear metal center, and one oxygen atom interacts with His-140. The a-carboxylate of the inhibitor interacts with Tyr-231. The proline side chain occupies a small substrate binding cavity formed by residues contributed from the loop that follows beta-strand 7 within the (beta/alpha)(8)-barrel. A total of 38 other proteins from cog1228 are predicted to have the same substrate profile based on conservation of the substrate binding residues. The structure of an evolutionarily related protein, Cc2672 from Caulobacter crecentus, was determined as a complex with the N-methylphosphonate derivative of L-arginine (PDB code 3MTW).

  DOI：

  10.1021/bi100897u
• 作为产物：
  描述：

  Fmoc-Pro-Pro-OMe 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以76%的产率得到N-芴甲氧羰基-脯氨酰-脯氨酸
  参考文献：
  名称：

  Gayathri; Gopi; Suresh Babu, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1998, vol. 37, # 2, p. 151 - 154

  摘要：

  DOI：

文献信息

• Solution-phase synthesis and evaluation of tetraproline chiral stationary phases
  作者：Zhi Dai、Guozhong Ye、Charles U. Pittman、Tingyu Li

  DOI：10.1002/chir.22001

  日期：2012.4

  solution‐phase synthesis of multigram amounts of two 9‐fluorenylmethoxycarbonyl (Fmoc)‐protected tetraproline peptides. These tetraproline peptides were then attached to amino derivatized silica gel. The replacement of the Fmoc group with the trimethylacetyl group lead to two tetraproline chiral stationary phases (CSPs). A comparison of the chromatographic behavior of these two solution‐phase‐synthesized

  开发了一种协议方案，用于溶液相合成多克数量的两个9-芴基甲氧基羰基（Fmoc）保护的四脯氨酸肽。然后将这些四脯氨酸肽连接到氨基衍生的硅胶上。用三甲基乙酰基取代Fmoc基团会导致两个四脯氨酸手性固定相（CSP）。将这两种溶液相合成的四脯氨酸CSP与通过逐步固相合成制备的CSP的色谱行为进行比较，结果表明，这三种溶液均具有相似的色谱性能，可分离53种模型分析物。这表明寡聚脯氨酸的溶液相合成具有良好的批次重现性，选择器均质性以及可能的低成本等特定优势，是寡聚脯氨酸CSP固相合成的可行替代方法。手性，2012年。©2012 Wiley Periodicals，Inc.。
• [EN] PEPTIDOMIMETIC AGENTS, SYNTHESIS AND USES THEREOF<br/>[FR] AGENTS PEPTIDOMIMÉTIQUES, SYNTHÈSE ET UTILISATIONS DE CEUX-CI
  申请人：FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH

  公开号：WO2020227588A1

  公开（公告）日：2020-11-12

  Compounds for use in synthesis of peptidomimetic agents; synthesis of peptidomimetic agents; peptidomimetic diagnostic and therapeutic agents; and uses of the compounds and peptidomimetic agents in drug discovery, diagnosis, prevention and treatment of diseases are described.

  描述了用于合成肽类模拟药物的化合物；合成肽类模拟药物；肽类模拟诊断和治疗剂；以及化合物和肽类模拟药物在药物发现、诊断、预防和治疗疾病中的用途。
• Preliminary Study of New Gallium-68 Radiolabeled Peptide Targeting NRP-1 to Detect Brain Metastases by Positron Emission Tomography
  作者：Albert Moussaron、Valérie Jouan-Hureaux、Charlotte Collet、Julien Pierson、Noémie Thomas、Laurence Choulier、Nicolas Veran、Matthieu Doyen、Philippe Arnoux、Fatiha Maskali、Dominique Dumas、Samir Acherar、Muriel Barberi-Heyob、Céline Frochot

  DOI：10.3390/molecules26237273

  日期：——

  Due to their very poor prognosis and a fatal outcome, secondary brain tumors are one of the biggest challenges in oncology today. From the point of view of the early diagnosis of these brain micro- and macro-tumors, the sensitivity and specificity of the diagnostic tools constitute an obstacle. Molecular imaging, such as Positron Emission Tomography (PET), is a promising technique but remains limited in the search for cerebral localizations, given the commercially available radiotracers. Indeed, the [18F]FDG PET remains constrained by the physiological fixation of the cerebral cortex, which hinders the visualization of cerebral metastases. Tumor angiogenesis is recognized as a crucial phenomenon in the progression of malignant tumors and is correlated with overexpression of the neuropilin-1 (NRP-1) receptor. Here, we describe the synthesis and the photophysical properties of the new gallium-68 radiolabeled peptide to target NRP-1. The KDKPPR peptide was coupled with gallium-68 anchored into a bifunctional NODAGA chelating agent, as well as Cy5 for fluorescence detection. The Cy5 absorbance spectra did not change, whereas the molar extinction coefficient (ε) decreased drastically. An enhancement of the fluorescence quantum yield (φF) could be observed due to the better water solubility of Cy5. [68Ga]Ga-NODAGA-K(Cy5)DKPPR was radiosynthesized efficiently, presented hydrophilic properties (log D = −1.86), and had high in vitro stability (>120 min). The molecular affinity and the cytotoxicity of this new chelated radiotracer were evaluated in vitro on endothelial cells (HUVEC) and MDA-MB-231 cancer cells (hormone-independent and triple-negative line) and in vivo on a brain model of metastasis in a nude rat using the MDA-MB-231 cell line. No in vitro toxicity has been observed. The in vivo preliminary experiments showed promising results, with a high contrast between the healthy brain and metastatic foci for [68Ga]Ga-NODAGA-K(Cy5)DKPPR.

  由于其非常不良的预后和致命的结果，继发性脑肿瘤是当今肿瘤学中最大的挑战之一。从早期诊断这些脑微小和宏观肿瘤的角度来看，诊断工具的敏感性和特异性构成了一个障碍。分子影像学，如正电子发射断层扫描（PET），是一种有前途的技术，但在寻找脑部定位方面仍然受到限制，因为商业上可用的放射示踪剂有限。事实上，[18F]FDG PET受到大脑皮层生理固定的限制，这阻碍了对脑转移的可视化。肿瘤血管生成被认为是恶性肿瘤进展中的关键现象，并与神经丝素-1（NRP-1）受体的过表达相关。在这里，我们描述了新的镓-68标记的肽以靶向NRP-1的合成和光物理性质。KDKPPR肽与镓-68结合到双功能NODAGA螯合剂中，同时与Cy5结合以进行荧光检测。Cy5吸收光谱没有改变，而摩尔消光系数（ε）急剧下降。由于Cy5更好的水溶性，可以观察到荧光量子产率（φF）的增加。[68Ga]Ga-NODAGA-K(Cy5)DKPPR在辐射合成时效率高，具有亲水性（log D = -1.86），并且具有高体外稳定性（>120分钟）。这种新螯合放射示踪剂的分子亲和力和细胞毒性在体外对内皮细胞（HUVEC）和MDA-MB-231癌细胞（激素非依赖性和三阴性系列）以及在裸鼠脑转移模型上的体内使用MDA-MB-231细胞系进行了评估。没有观察到体外毒性。体内初步实验显示了令人满意的结果，[68Ga]Ga-NODAGA-K(Cy5)DKPPR在健康大脑和转移灶之间具有高对比度。
• Sustainable, cost-efficient manufacturing of therapeutic peptides using chemo-enzymatic peptide synthesis (CEPS)
  作者：Jan Pawlas、Timo Nuijens、Jonas Persson、Thomas Svensson、Marcel Schmidt、Ana Toplak、Mikael Nilsson、Jon H. Rasmussen

  DOI：10.1039/c9gc03600h

  日期：——

  Exemplified by antidiabetic exenatide CEPS provides a highly efficient, easily scalable biocatalytic route to manufacture therapeutic peptides.

  由抗糖尿病荷尔蒙exenatide示范，CEPS提供了一条高效、易于扩展的生物催化途径，用于制造治疗肽。
• An improved preparation of a tertiary alcohol proline linker and its use in a synthesis of mosquito oostatic hormone
  作者：Jan Kochansky、R.M. Wagner

  DOI：10.1016/s0040-4039(00)74702-2

  日期：1992.12

  An improved synthesis of 4-(3′-hydroxy-3′-methylbutyl)phenoxyacetic acid was developed using THF to overcome solubility problems initially encountered in trying to reproduce the published preparation. This hydroxyacid linker was coupled to aminomethyl polystyrene resin and used for a synthesis of the mosquito oostatic hormone by the Fmoc protocol. Attempts to prepare this insect peptide by other techniques

  使用THF开发了一种改进的4-（3'-羟基-3'-甲基丁基）苯氧基乙酸的合成方法，以克服在尝试复制公开的制剂时最初遇到的溶解性问题。该羟基酸接头与氨基甲基聚苯乙烯树脂偶联，并通过Fmoc方案用于合成蚊子的排卵激素。由于从树脂中损失了环-Pro 2，通过其他技术制备这种昆虫肽的尝试失败了。